Project Summary This application is for a predoctoral fellowship awarded by the National Institute of Neurological Disorders and Stroke to scientific trainees. The applicant is a trainee of the Medical Scientist Training Program at the Perelman School of Medicine at the University of Pennsylvania. This award would help her achieve her career goal of becoming an academic Principal Investigator studying the relationship of sleep to neurological disease. Nearly all species exhibit increased sleep amount in early life, known as sleep ontogeny?, which is thought to facilitate brain structural maturation. Childhood sleep disturbances portend later neurocognitive deficits and are highly prevalent across neurobehavioral disorders. Further, sleep abnormalities during development may drive aberrant neural circuit formation underlying many neurobehavioral disorders. Improving sleep by targeting regulatory pathways could thus represent a new therapeutic avenue for such illnesses. However, the molecular and genetic factors regulating early life sleep remain unknown, hindering design of compelling sleep-related strategies. Sleep in the genetically accessible fruit fly, Drosophila melanogaster, shares many features with human sleep, including increased sleep in early life and common genetic control, suggesting conservation of ontogeny-regulating genes. We recently demonstrated that high sleep amounts in early life result from developmentally regulated changes in dopaminergic signaling. Despite knowledge of involved circuitry, the genetic factors controlling early life sleep remain unknown. The goal of this project is to use Drosophila to understand the genetic basis of sleep ontogeny. Preliminary data strongly suggests that the POU domain transcription factor, pdm3, controls sleep ontogeny. Using well-validated sleep monitoring assays and the myriad genetic techniques available in Drosophila, the role of pdm3 will be examined in two aims. Aim 1 will ascertain when during neural development pdm3 acts to control sleep ontogeny and dissect nuanced behavioral features of sleep ontogenetic change in the setting of pdm3 ablation. Aim 2 will determine circuit- specificity of pdm3 action and test the hypothesis that pdm3 is required for the cellular encoding of high sleep drive in early life. The expected results will deepen our understanding of the conserved phenomenon of sleep ontogeny, providing a platform for investigating behavioral sequelae of abnormal sleep during development and facilitating the design of novel sleep-focused treatment strategies for neurobehavioral disorders.